Jonathan R. Carapetis

Objectives: Despite increasing urbanisation, little is known about skin health for urban-living Aboriginal children and young people (CYP, aged <18 years). This study aimed to investigate the primary care burden and clinical characteristics of skin conditions in this cohort. Method: A one-year retrospective cohort study of urban-living Aboriginal CYP presenting for general practitioner (GP) consultation at an Aboriginal Community Controlled Health Organisation (ACCHO) was conducted. Results: At least one dermatological diagnosis was made in 27% (253/939) of GP face-to-face consultations for the 585 urban-living Aboriginal CYP included. Infections and dermatitis accounted for 54% (152/284) and 18% (50/284) of all dermatological diagnoses, respectively. Bacterial skin infection (BSI) cumulative incidence was 13% (74/585; 95% CI 10-16%), with recurrent BSI affecting <1% (5/585; 95% CI 0.3-2%) and hospitalisation required in 1% (1/82; 95% CI 0.06-7%) of incident BSI cases. Discussion: We present a culturally secure, multidisciplinary skin health assessment model within an urban ACCHO, where dermatological conditions account for a significant proportion of GP workload.

Although benzylpenicillin (penicillin G) is listed by the World Health Organization as an Essential Medicine, dose optimization is a persistent challenge, especially for long-acting intramuscular formulations. Maintaining sustained antibiotic exposure at target concentrations is crucial for secondary chemoprophylaxis of rheumatic heart disease and treatment of syphilis. This study compared the pharmacokinetic profile of continuous low-dose benzylpenicillin infusions with a standard-dose bolus and evaluated which renal function marker (serum creatinine, cystatin C, or combined e-glomerular filtration rate [eGFR]) best predicted clearance. Healthy adult volunteers received a single 600 mg IV benzylpenicillin bolus followed by randomization to continuous infusions targeting steady-state concentrations of 3, 6, 9, 12, or 20 ng/mL. Plasma benzylpenicillin concentrations were measured by liquid chromatography-mass spectrometry. Population pharmacokinetic analysis was performed using NONMEM by incorporating both bolus and infusion data, and various GFR estimations were evaluated as covariates for clearance. Data from 72 participants were analyzed, including 504 bolus and 389 continuous infusion samples. A two-compartment model improved fit when the ratio of central volume of distribution between bolus and low-dose infusion was incorporated, and clearance differences at steady state plasma concentration of 3 ng/mL were accounted for. Of the GFR estimations, cystatin C-based eGFR significantly enhanced model fit compared with creatinine-based equations. Benzylpenicillin pharmacokinetics at very low concentrations demonstrated both a higher volume of distribution and increased clearance. Cystatin C-based eGFR may more accurately predict benzylpenicillin clearance, enabling precision dosing for long-acting preparations used for treatment of syphilis and prevention of rheumatic fever.

This paper presents a comprehensive cardiac safety framework for early clinical development of Streptococcus pyogenes (Group A Streptococcus) vaccines, endorsed by the Strep A Vaccine Global Consortium (SAVAC) and the Australian Strep A Vaccine Initiative (ASAVI). Given historical concerns about vaccine-associated acute rheumatic fever (ARF), we have established standardized echocardiography protocols integrated with clinical assessment for monitoring cardiac safety in early-phase vaccine trials. We recommend that the Modified Jones Criteria for ARF should be the primary focus for cardiac Adverse Events of Special Interest (AESI) monitoring in S. pyogenes vaccine trials, with echocardiography utilized within this clinical context. Two echocardiography protocols-comprehensive for baseline screening and diagnostic confirmation and abbreviated for interval monitoring-should be performed using full-capability equipment by certified professionals. The framework includes specific exclusion criteria for trial participants, active and passive surveillance for ARF symptoms, and a structured approach to investigating suspected cases. This pragmatic approach enables advancement of S. pyogenes vaccine clinical development with appropriate safety oversight while maintaining operational feasibility. While designed for phase 1 and 2 trials in low-endemic settings, these recommendations provide a foundation that can be adapted for later-phase trials in high-endemic regions as vaccine development progresses.

Aboriginal children and families contend with higher rates of preventable infectious diseases that can be attributed to their immediate living environment. The environments in which children spend most of their time are their homes and schools. We aimed to understand the opportunities in the school setting to support student skin health and wellbeing through environmental health activities, how these activities were completed, and the barriers to their implementation. Recognising the importance of healthy skin for educational success, this work was embedded within a larger cluster randomised stepped-wedge Trial aimed at reducing the rate of skin infections among Aboriginal children living in the Kimberley region of Western Australia by 50 %. We used qualitative data collected via a culturally appropriate yarning methodology during trial evaluation interviews. The data from 35 yarns with 41 individuals were thematically analysed. Data indicated that schools serve as a hub of health and hygiene support and maintenance, with school staff balancing teaching responsibilities while also meeting the basic health and wellbeing needs of students. Uncertainties regarding funding and policies governing these activities remained; ongoing exploration is required. Staff in remote Kimberley schools devote substantial time and resources to supporting student hygiene needs, often stepping in when health infrastructure at home is inadequate. These activities are seen as necessary to support student wellbeing and participation in learning. While schools are well-positioned to respond in this way, these responsibilities extend beyond their core role and place additional pressure on staff and budgets. There is a need to better understand how such work is resourced and to consider how policy and funding frameworks might more formally support it.

Introduction: Rheumatic heart disease (RHD) is underdiagnosed globally resulting in missed treatment opportunities and adverse clinical outcomes. We describe the protocol for a study which aims to co-design, implement and conduct an evaluation of a task-sharing approach to echocardiographic active case finding for early detection and management of RHD in high-risk settings in Australia and Timor-Leste. Methods and analysis: Echocardiograms will be obtained by trained local staff using hand-held echocardiographic devices employing the 'Single Parasternal Long Axis view with a Sweep of the Heart' (SPLASH) technique and interpreted by experts remote from the site of acquisition. Approximately 1500 children and pregnant women will be screened across high-risk communities in Australia and Timor-Leste over an 18-month period. The study will use a type II effectiveness-implementation hybrid design. A tailored package of implementation strategies will be co-designed with communities and health services and mapped onto a Theory of Change framework. The clinical effectiveness will be assessed as the change in the proportion of the target population that are prescribed secondary prophylaxis for RHD by the end of the study compared with baseline. The implementation will be assessed as the adoption, penetration, sustainability, fidelity and cost of the programme with a mixed-methods theory-based and economic evaluation. Data will include numbers of normal, abnormal and uninterpretable SPLASH echocardiograms obtained, numbers of participants progressing through the cascade of care, interviews with staff and programme costs. Ethics and dissemination: Ethical approval has been obtained from the Human Research Ethics Committee of the NT Department of Health and Menzies School of Health Research, Darwin (HREC-2022-4479), the Western Australian Aboriginal Health Ethics Committee (HREC-1237) and the Instituto Nasional Saude Publika Timor-Leste Ethics and Technical Committee (03-UEPD/INSP-TL/V/2023). Informed consent is required to be enrolled. Study findings will be disseminated in the communities involved and submitted for publication. Trial registration number: NCT06002243.